Lysine--tRNA ligase

Lysine–tRNA ligase (KARS1) is an aminoacyl-tRNA synthetase that catalyzes the attachment of lysine to its cognate tRNA, a fundamental step in protein synthesis (UniProt: Q15046). The protein also functions as a secreted signaling molecule activating immune responses in monocytes and macrophages, and participates in synthesis of the signaling molecule diadenosine tetraphosphate, which regulates MITF transcriptional activity. Additionally, KARS1 interacts with HIV-1 GAG protein during viral replication.

KARS1 is associated with several neurological disorders in UniProt, including autosomal recessive forms of Charcot-Marie-Tooth disease, non-syndromic deafness, and progressive leukoencephalopathy with infantile or adult onset. These conditions reflect the protein's critical role in protein synthesis and nervous system function.

In Alzheimer's disease, KARS1 shows increased abundance in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics), with a mean log2 fold-change of 0.27 across analyzed subcellular fractions. This modest upregulation may reflect compensatory responses or altered protein synthesis dynamics in AD pathology.